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In the design and optimization of nanofluids, it is crucial to investigate and characterize the thermal conductivity enhancement mechanisms and their influencing factors. Although the effect of the “liquid film” on the thermal conductivity of the solid–liquid interface in nanofluids has been extensively studied, most of the research in this area has examined metal–water nanofluids or Ar-based nanofluids. In this work, non-equilibrium molecular dynamics is utilized to explore the mechanism of thermal conductivity enhancement in TiO2–water nanofluids. It is noted that a distinct interfacial layer is formed within 5 Å from the nanoparticle surface. As the nanoparticle size increases, the number density also increases, resulting in a corresponding increase in the thermal conductivity. Moreover, adding 1% TiO2 nanoparticles to water leads to an increase in thermal conductivity of 1.5–3%. Notably, the interfacial layer thickness remains relatively constant with the change in temperature. The Materials Studio analysis results indicated that the water molecule will have stable chemisorption on the titanium dioxide surface with an adsorption energy of approximately −0.96 eV. The findings of this study offer new insights and useful information to support the selection of nanomaterials for the preparation of convective systems.

The influence of nanoparticle shape, volume fraction, and temperature on the thermal properties of nanofluids plays a pivotal role in engineering applications. However, there remains a considerable lack of systematic research comprehensively considering these factors to study the similarities and differences in the thermal properties of nanofluids composed of metals and their oxides and to conduct in-depth analyses of their internal mechanisms and characteristics. In this study, molecular dynamics simulations were conducted, employing reversing perturbation non-equilibrium molecular dynamics and non-equilibrium molecular dynamics methods. The thermal conductivity and viscosity of Al–Ar and Al2O3–Ar nanofluids were thoroughly investigated under the various influencing factors. Results reveal that under identical conditions, the thermal conductivity of Al–Ar nanofluid surpasses that of Al2O3–Ar nanofluid, exemplified by values such as 0.1832 W/m K (Al–Ar, 1.5%, cylinder, 86 K) versus 0.17745 W/m K (Al2O3–Ar, 1.5%, cylinder, 86 K). Furthermore, the viscosity of Al–Ar nanofluid is lower than that of Al2O3–Ar nanofluid, demonstrated by values such as 0.0004882 Pa S (Al–Ar nanofluid, 86 K, 2.5%, platelets) compared to 0.008975 Pa S (Al2O3–Ar nanofluid, 86 K, 2.5%, platelets). Subsequently, this study analyzed the difference in thermal conductivity between the two nanofluids from the perspective of microscale interface heat conduction by comparing the phonon density of states curves of Al, Ar, and Al2O3 in the two nanofluids for overlap. Subsequently, through radial distribution function analysis, the viscosity difference between Al–Ar and Al2O3–Ar nanofluids is explained based on nanofluid–solid interface and microstructural considerations. This research addresses the comprehensive lack of comparative studies on the thermal properties of nanofluids formed by metals and their oxides. The internal mechanisms underlying the thermal property differences of nanofluids formed by metals and their oxides were revealed from a microscopic perspective, which holds significant implications for the engineering applications of nanofluids.

The aging of pancreatic beta cells is closely associated with various diseases, such as impaired glucose tolerance, yet the underlying regulatory mechanisms remain unclear. In this study, we screened young and aged mouse pancreatic beta cells' high-throughput sequencing data from the GEO public database. Utilizing bioinformatics techniques, we identified the key regulatory factor YY1 in the aging process of pancreatic islets. We observed a significant decrease in the expression of YY1 in a D-gal-induced mouse model of pancreatic aging and an H2O2-induced MIN6 cell model of aging. Moreover, both vivo and vitro models, we found that the YY1 agonist eudesmin (EDN) improved glucose intolerance in mice, alleviated aging of pancreatic beta cells, and downregulated the expression of cell cycle protein P21. Mechanistically, we discovered that EDN inhibited the P38/JNK MAPK pathway in aging cells. In summary, our study confirms the regulatory role of the transcription factor YY1 in the aging process of pancreatic beta cells. This finding may provide a new approach for the clinical treatment of pancreatic aging-related diseases such as impaired glucose tolerance or diabetes.

Background: The efficacy of immune checkpoint inhibitors (ICIs) in cancer patients taking anti-hypertensive drugs is still not well established. Objective: To elucidate the effect of anti-hypertensive drugs on the clinical outcome of cancer patients receiving immunotherapy. Design: A retrospective cohort study and meta-analysis. Method: We conducted a real-world retrospective study of cancer patients treated with immunotherapy at two tertiary centers between January 2019 and June 2023, with primary outcomes being overall survival (OS) and progression-free survival (PFS). In addition, we performed a meta-analysis to synthesize currently relevant clinical studies. Results: A retrospective clinical study of 336 patients from 2 centers suggested that the use of anti-hypertensive drugs was related to a preferable OS (hazard ratio (HR) = 0.55, 95% confidence interval (CI): 0.33–0.90) compared to non-users. For PFS, no significant correlation was detected (HR = 0.71, 95% CI: 0.49–1.03). Further analysis revealed that renin–angiotensin system inhibitor (RASi) and calcium channel blocker (CCB) have a synergistic effect with ICIs. In addition, subgroup analysis found that the benefits of RASi or CCB in combination with ICIs are greater in women or patients ⩾65 years of age. There was better disease control in lung cancer patients using RASi, and a significantly longer OS was observed in patients with gastrointestinal tumors taking CCB. Meta-analysis suggested that anti-hypertensive drugs were associated with improved OS, but only the combination of RASi and immunotherapy showed a synergistic effect. No significant correlation with OS was found for other anti-hypertensive drugs, and there was no overall positive effect on PFS. Conclusion: Our study found that use of anti-hypertensive drugs, particularly RASi or CCB, was associated with improved OS in patients undergoing immunotherapy. The synergistic effects of RASi or CCB with ICIs were more pronounced in females or elderly. RASi or CCB exhibited different benefits in various types of tumors. These findings provide valuable insights for treating cancer patients with hypertension.

ObjectiveDepression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression.MethodsForty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons.ResultsCompared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex.ConclusionAfter 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.

[This corrects the article DOI: 10.1371/journal.pone.0268007.].

ObjectiveThe aim of this study was to explore the predictive value of the ratio of procalcitonin (PCT) in serum to Simpson’s dominance index (SDI) in bronchoalveolar lavage fluid (BALF), in short-term prognosis of patients with severe bacterial pneumonia (SBP).MethodsThis is a retrospective review of case materials of 110 patients with SBP who selected BALF metagenomic next-generation sequencing technique in the intensive care unit (ICU) of the Affiliated Hospital of Yangzhou University from January 2019 and July 2022. Based on the acute physiology and chronic health status score II, within 24 h after admission to the ICU, patients were divided into a non-critical group (n = 40) and a critical group (n = 70). Taking death caused by bacterial pneumonia as the endpoint event, the 28-day prognosis was recorded, and the patients were divided into a survival group (n = 76) and a death group (n = 34). The SDI, PCT, C-reactive protein (CRP), PCT/SDI, and CRP/SDI were compared and analyzed.ResultsCompared with the non-critical group, the critical group had a higher PCT level, a greater PCT/SDI ratio, a longer ventilator-assisted ventilation time (VAVT), and more deaths in 28 days. Compared with the survivors, the death group had a higher PCT level, a lower SDI level, and a greater PCT/SDI ratio. The SDI level was significantly negatively correlated with the VAVT (r = −0.675, p < 0.05), while the PCT level, ratio of PCT/SDI, and ratio of CRP/SDI were remarkably positively correlated with VAVT (r = 0.669, 0.749, and 0.718, respectively, p < 0.05). The receiver operating characteristic (ROC) curves analysis showed that the area under ROC curves of PCT/SDI predicting patient death within 28 days was 0.851, followed by PCT + SDI, PCT, SDI, and CRP/SDI (0.845, 0.811, 0.778, and 0.720, respectively). The sensitivity and specificity of PCT/SDI for predicting death were 94.1% and 65.8%, respectively, at the optimal value (11.56). Cox regression analysis displayed that PCT/SDI (HR = 1.562; 95% CI: 1.271 to 1.920; p = 0.039) and PCT (HR = 1.148; 95% CI: 1.105 to 1.314; p = 0.015) were independent predictors of death in patients.ConclusionThe ratio of PCT/SDI was a more valuable marker in predicting the 28-day prognosis in patients with SBP.

For post-menopausal women, stroke is complicated by the variable effects of estrogen therapy and the age-related therapeutic consequences involved. Estrogen therapy has been shown to have an age-dimorphic effect, which is neuroprotective in young females, but non-neuroprotective, even neurotoxic in acyclic females. We hypothesized that arterial baroreflex (ABR) and its downstream acetylcholine-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammatory pathways are involved in estrogen efficacy toward cerebral ischemic damage. Our data showed that estrogen supplements contributed to ABR improvement and neuroprotection in adult, not aged, ovariectomized (OVX) rats. In adult rats, OVX-induced estrogen deficiency aggravated middle cerebral artery occlusion (MCAO), which induced brain infarction and reduced ABR function, with decreased α7nAChR expression of the brain and exaggerated inflammation following MCAO; these effects were significantly prevented by supplementation with estrogen. ABR impairment by sinoaortic denervation partly attenuated the estrogen effect on baroreflex sensitivity (BRS) and ischemic damage in adult rats, as well as α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR anti-inflammatory pathways are involved in the neuroprotection of estrogen in adult OVX rats. In contrast, aged rats exhibited more severe ischemic damage and inflammatory response than adult rats, as well as poorer baroreflex function and lower α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR and post-ischemic inflammation. Most importantly, ketanserin restored ABR function and significantly postponed the onset of stroke in aged female strokeprone spontaneously hypertensive rats, whereas estrogen treatment failed to delay the development of stroke. Our findings reveal that estrogen is protective against ischemic stroke (IS) in adult female rats and that ABR played a role in this beneficial action. Dysfunction of ABR and unresponsiveness to estrogen in aged female rats may contribute to a reduced estrogen efficacy against cerebral ischemia.

Multi-target X-ray tube is a new type X-ray source, and can be applied in many fields such as sensitive X-ray fluorescence analysis and medical imaging. In this work, we report an electric field modulation multi-target X-ray tube, which contains four targets (Cr, Ni, Au, Mo) coated on a Beryllium (Be) window. A four-valve electric field deflector was developed to deflect the electron beam to bombard the corresponding targets. Particle dynamics analysis software was employed to simulate the particle tracking of electron beam. The results show that the 30 keV electron beam could get a 6.7 mm displacement on the target plane by 105 V/m electric field. The focus areas are about 2 mm × 5 mm and 4 mm × 2.5 mm after deflection in two directions. Thermal behavior calculated by ANSYS shows that the designed target assembly could withstand a 10 W continuous power. The optimum target thicknesses and emission spectra were obtained by Geant4 when the thickness of Be window was 300 μm and the electron beam incident angle was 0.141 rad. The results indicate that this multi-target X-ray tube could provide different X-ray sources effectively.

The mechanisms of thermal conductivity enhancement and the factors influencing viscosity are of great interest in the study of nanofluids, while molecular dynamics (MD) simulations considering nanofluids provide more accurate predictions of microscopic properties than conventional experimental studies. MD simulations of non-equilibrium molecular dynamics and reversing perturbation non-equilibrium molecular dynamics methods were used to study thermal conductivity and viscosity, taking into account a variety of influencing factors, as well as nanoparticle material and volume fraction. Through the analysis of the number density distribution, radial distribution function (RDF), and mean square displacement (MSD), the influences of different nanoparticles (Ag, Cu, Au, and Fe) were described and investigated: Ag particles contribute to 47.0% increase in thermal conductivity of 2.5 vol% nanofluids; Au particles improved the viscosity of 2.5 vol% nanofluids by 20.2%; the number density distribution showed positive linear relationship with the atomic mass; the results of MSD and RDF (mean square displacement and radial distribution function) in combination indicated a positive effect of interfacial nanolayer. The results of this research provide important perspectives for comprehending the impacts of multiple nanoparticles on the micro-thermal properties of nanofluids and also highlight the simulation potential of Au–Ar nanofluids.

During severe nuclear accidents, radioactive materials are expected to be released into the atmosphere. Estimating the source term plays a significant role in assessing the consequences of an accident to assist in actioning a proper emergency response. However, it is difficult to obtain information on the source term directly through the instruments in the reactor because of the unpredictable conditions induced by the accident. In this study, a deep learning-based method to estimate the source term with field environmental monitoring data, which utilizes the bagging method to fuse models based on the temporal convolutional network (TCN) and two-dimensional convolutional neural network (2D-CNN), was developed. To reduce the complexity of the model, the particle swarm optimization algorithm was used to optimize the parameters in the fusion model. Seven typical radionuclides (Kr-88, I-131, Te-132, Xe-133, Cs-137, Ba-140, and Ce-144) were set as mixed source terms, and the International Radiological Assessment System was used to generate model training data. The results indicated that the average prediction error of the fusion model for the seven nuclides in the test set was less than 10%, which significantly improved the estimation accuracy compared with the results obtained by TCN or 2D-CNN. Noise analysis revealed the fusion model to be robust, having potential applicability toward more complex nuclear accident scenarios.

BaF2–TiO2 nanocomposite material (hereinafter called the composite) was prepared by a sol–gel method. The composite surface area, morphology and structure were characterized by Brunauer–Emmett–Teller method, X-ray diffraction analysis and a scanning electron microscopy. The results showed that BaF2 and TiO2 form a PN-like structure on the surface of the composite. Composites were used to catalyse the degradation of methyl orange by irradiation with ultraviolet light, γ-rays and an electron beam (EB). It was demonstrated that the composite is found to be more efficient than the prepared TiO2 and commercial P25 in the degradation of methyl orange under γ-irradiation. Increasing the composite catalyst concentration within a certain range can effectively improve the decolorization rate of the methyl orange solution. However, when the composite material is used to catalyse the degradation of organic matter in the presence of ultraviolet light or 10 MeV EB irradiation, the catalytic effect is poor or substantially ineffective. In addition, a hybrid mechanism is proposed; BaF2 absorbs γ-rays to generate radioluminescence and further excites TiO2 to generate photo-charges. Due to the heterojunction effect, the resulting photo-charge will produce more active particles. This seems to be a possible mechanism to explain γ-irradiation's catalytic behaviour.

Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone (LM49-API), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of LM49-API and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of LM49-API. Its finalized preparation process was further validated at 329−410 g scale-up production in 53.4−57.1% overall yield with 99.95−99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production. LM49-API-imC and LM49-API-imX were identified as the main single impurities in LM49-API, with the content controlled to be less than 0.03%.

Marketing accountability and the measurement of marketing performance have long been reported as a significant challenge for management globally. To address the increasing demand for marketing accountability, companies across the world are investing resources in developing and improving their marketing performance measurement (MPM) practices. MPM practices in Irish firms were reported to be less well developed than those reported in other countries. This study aims to investigate if and how MPM practices have changed since then, by means of a comparative analysis which contrasts secondary data collected by O'Sullivan in 2007 and primary data collected in 2015. This study also seeks to examine the impact of MPM practices on firms’ marketing capabilities and firm performance. Based on survey data collected from 210 Irish managers, this study finds that companies adopting comprehensive MPM practices tend to develop enhanced marketing capabilities and achieve better firm performance than those adopting less comprehensive MPM practices.

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

In this paper, we study the non-stationary parallel multisplitting two-stage iterative methods with selfadaptive weighting matrices for solving a linear system whose coefficient matrix is symmetric positive definite. Two choices of Self-adaptive weighting matrices are given, especially, the nonnegativity is eliminated. Moreover, we prove the convergence of the non-stationary parallel multisplitting two-stage iterative methods with self-adaptive weighting matrices. Finally, the numerical comparisons of several self-adaptive nonstationary parallel multisplitting two-stage iterative methods are shown.

A series of novel furan-2-yl(phenyl)methanone derivatives were synthesized, and their structures were established on the basis of 1H-NMR, 13C-NMR and mass spectral data. All the prepared compounds were screened for their in vitro protein tyrosine kinase inhibitory activity and several new derivatives exhibited promising activity, which, in some cases, was identical to, or even better than that of genistein, a positive reference compound. The preliminary structure-activity relationships of these compounds were investigated and are discussed.

We previously reported 5,2’-dibromo-2,4’,5’-trihydroxydiphenylmethanoe (LM49), a bromophenol analogue that shows strong protection from oxidative stress injury owing to its superior anti-inflammatory, antioxidant, and anti-apoptotic properties. A series of novel nitrogen-containing heterocycle bromophenols were herein synthesized by introducing substituted piperidine, piperazine, and imidazole to modify 2-position of the lead compound LM49. By further evaluating their cytoprotective activity against H2O2 induced injury in EA.hy926 cells, 14 target bromophenols showed moderate-to-potent activity with EC50 values in the range of 0.9–6.3 μM, which were stronger than that of quercetin (EC50: 18.0 μM), a positive reference compound. Of these, the most potent compound 22b is a piperazine bromophenol with an EC50 value of 0.9 μM equivalent to the LM49. Molecular docking studies were subsequently performed to deduce the affinity and binding mode of derived halophenols toward the Keap1 Kelch domain, the docking results exhibited that the small molecule 22b is well accommodated by the bound region of Keap1-Kelch and Nrf2 through stable hydrogen bonds and hydrophobic interaction, which contributed to the enhancement of affinity and stability between the ligand and receptor. The above facts suggest that 22b is a promising pharmacological candidate for further cardiovascular drug development. Moreover, the targeting Keap1-Nrf2 protein-protein interaction may be an emerging strategy for halophenols to selectively and effectively activate Nrf2 triggering downstream protective genes defending against injury.